A comprehensive response

International Conference highlights need for simultaneous treatment and prevention efforts

Since the World AIDS conference was held in Durban more than five years ago, there has been a sustained international interest in making antiretroviral (ARV) therapy available to people in developing countries. Thanks to a collection of global initiatives, including the World Health Organization's (WHO) '3 by 5' Initiative and the Global Fund to Fight AIDS, Tuberculosis, and Malaria, the scaling up of treatment programs is finally occurring. Now researchers are reinforcing the importance of prevention messages and new prevention strategies for slowing the spread of HIV.

Thousands of delegates gathered recently in Rio de Janeiro, Brazil for the 3 rd International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment. Speakers throughout the four-day conference emphasized how treatment access can promote HIV prevention efforts. When ARVs are unavailable fewer people are willing to be tested for HIV infection and this makes it more difficult to emphasize prevention messages. Both treatment programs and ARV trials provide an opportunity for healthcare workers to offer a variety of prevention services and to discuss ways that individuals can reduce their risk (see Primer, this issue). This includes offering people voluntary counseling and testing (VCT; see April Primer on Understanding Research Voluntary Counseling and Testing). The positive effect that treatment access has on VCT rates is illustrated in the recent report (www.who.int/3by5/progressreportJune2005) from the WHO and the United Nations Joint Programme on HIV/AIDS (UNAIDS). The report highlights a district in Uganda where there was a 27-fold increase in the number of people coming in for VCT services when ARV therapy was introduced.

The researchers and community representatives in Rio repeatedly acknowledged that even though the need for treatment remains great, HIV prevention efforts should occur at the same time because ARVs alone will not control the epidemic. The conference highlighted several areas of prevention, including the increased importance of risk reduction efforts for injection drug users (IDUs), exploring novel strategies like male circumcision, and the need to continue research into the development of long-term options like vaccines.

Risk among IDUs soars

In a plenary talk on emerging HIV epidemics Chris Beyrer of Johns Hopkins University in the US offered a sobering description of the dire conditions facing IDUs in several countries in Eurasia (Eastern Europe and Central Asia). Despite an exploding number of new HIV infections in this region there are very few treatment and prevention programs.

Beyrer pinpointed 11 countries as places where explosive HIV epidemics are in progress. Official statistics estimate that currently 1.4 million people in the former countries of the Soviet Union are HIV infected, along with 1.1 million in China and Eastern Asia. The majority of these new infections are occurring among IDUs and the spread of the epidemic is aggravated by the lack of prevention programs to discourage IDUs from sharing syringes.

Tajikistan, the poorest country of the former Soviet bloc, is struggling to cope with a growing epidemic among IDUs yet there are currently no programs offering free access to ARVs and only a single non-governmental organization (The Open Society) is working on HIV prevention. The gross domestic product per capita was only US$179 in 2000, making it poorer than many African countries, and as much as half of all economic activity there is linked to drug sales. “While we are responding globally with access to treatment, HIV is spreading in new regions,” says Beyrer. “A very rapid HIV epidemic is now unfolding where very little prevention is happening.”

Needle-exchange programs or drug substitution programs that use non-addictive drugs like methadone or buprenophrine to wean people from heroin addiction are effective in reducing the transmission of HIV among IDUs. But only an estimated 10% of IDUs worldwide have access to needle-exchange programs, even with the recent expansion of prevention efforts in some countries like China where the government just recently loosened restrictions. The availability of programs is also limited by funding restrictions such as those in the US President’s Emergency Plan for AIDS Relief (PEPFAR) that restrict grant money from being used to fund syringe exchange. “We need to implement programs that we already know work. Unfortunately they have been very hard to start, despite mounds of scientific evidence that show they are effective,” says Beyrer.

Beyrer is also discouraged by the exclusion of IDUs from many of the global treatment programs. He points out that throughout Eurasia IDUs were the first groups to become HIV infected and therefore should be overrepresented in the populations receiving treatment, but this is not the case. “Even where policy allows, the de-facto reality is that people don’t get into treatment programs. It’s a terrible way to approach public health because you are isolating the people at highest risk.”

Some countries, such as Canada, are exploring innovative options to make injection drug use safer. Vancouver opened the first supervised injection facility in the Americas to address risk behaviors among the city’s large IDU population. In Rio Mark Tyndall of the BC Center for Excellence in HIV/AIDS provided an update on the center’s first 18 months. He reported that there were 15,000 different visitors to the site, which offers needle exchange, provides visitors with information on safe injection practices, and has nurses on hand to supervise injections. Counselors are also available and they can provide referrals to drug detoxification centers in the city.

The Vancouver site is modeled after similar locations in Europe and Australia, which have a good track record at reducing HIV transmission among visitors to the sites. In Vancouver, the HIV transmission rate among IDUs that come to the site continues to be high at around 30%. Visitors were, however, one third less likely to share needles.

Cutting sexual transmission

One of the biggest news stories at the conference came when a group of French researchers presented results from the first study to offer male circumcision to trial volunteers and then follow them to find out what effect this has on the female-to-male transmission of HIV. Bertran Auvert from the French national institute for medical research (INSERM) presented data from a study sponsored by the French National Agency for AIDS Research (ANRS) that found that adult male circumcision gave a 65% rate of protection from HIV infection.

Researchers have long thought that circumcision could be protective because it reduces the surface area available for transmission and encourages a toughening of the surrounding skin. The foreskin is also home to a high density of immune cells known as dendritic cells that could facilitate the transmission of HIV. This new study confirmed the results of more than 30 previous studies where researchers observed groups of both circumcised and uncircumcised men without actually performing the procedure. But these observational studies predicted a less dramatic effect.

This study enrolled over 3,000 men between the ages of 18 and 24 in an urban area on the outskirts of Johannesburg, known as Orange Farm. The men were selected randomly to either be circumcised immediately or to delay circumcision until after 21 months. Both groups received intensive counseling on how to reduce their risk for HIV infection and were treated for sexually-transmitted diseases at each study visit. Of 69 new HIV infections during the trial, 51 occurred in the uncircumcised group and only 18 in the circumcised men.

While many in the field of HIV prevention were excited by this result, the study investigators stressed the need for caution. Officials from the WHO and UNAIDS urged governments to await the results of similar ongoing studies before making official recommendations on circumcision. “More research is needed to confirm the reproducibility of these results in differing social and cultural contexts,” says Catherine Hankins of UNAIDS.

The Bill & Melinda Gates Foundation is sponsoring a trial in Uganda that is enrolling 800 HIV discordant couples where the man is HIV infected to monitor the effects of circumcision on male-to-female transmission. The other trials are sponsored by the US National Institutes of Health. Results from these trials are not expected until at least 2007.

Although circumcision is widely regarded as simple and safe, it is a surgical procedure and offering this intervention on a large scale would be difficult. The circumcisions in the setting of a clinical trial were done in proper medical facilities by trained surgeons, but this may not always be possible. Many public health experts fear that the high rate of protection offered in the South African study could encourage men to have unsafe circumcisions outside of medical facilities, which could put them at greater risk of HIV infection. WHO is currently formulating guidelines on safe circumcision practices to avoid this situation.

Researchers are also concerned that circumcised men could feel a false sense of protection after circumcision and therefore increase their risk behaviors. If circumcised men increase their number of sexual partners or stop using condoms it could moderate the protective effect. This is a concern for all HIV prevention trials. “Any new prevention tool should not undermine existing prevention programs,” adds Hankins.

There are also many unanswered questions about how acceptable circumcision will be within cultures and religions that typically discourage this practice. The French researchers conducted studies to determine the acceptability of circumcision in this area of South Africa and found that 70% of men were willing to undergo this surgical procedure if it was proven to prevent HIV infection.

“If this trial is confirmed by others, then it would be an important advance for prevention,” said Helene Gayle, president of the IAS. “But it should not be implemented until we have further information. There is no one thing that is going to make all the difference in prevention.”